A rat model is being developed to investigate the potential mechanisms by which maternal exposure to chemicals during pregnancy alters fetal respiratory tract development, and postnatal function of the respiratory tract. A major emphasis of this project is to evaluate alterations in pulmonary function resulting from in utero chemical exposure. Preliminary data suggest that in utero exposure to CdC12 may inhibit surfactant production in the fetal lung possibly by interfering with glycogen utilization. Studies are planned to investigate further the mechanism of surfactant inhibition, by measurement of lung changes in glycogen, and expression of surfactant apoprotein mRNA in fetal and neonatal lungs. To determine if irreversible effects are caused by in utero exposure, neonates at various ages will be evaluated for abnormalities in histological and biochemical indices of pulmonary development, and abnormal changes in pulmonary function in response to chemical challenge. Methods are being developed to measure biochemical changes in the lung at various time points. In addition, a whole-body plethysmograph is being developed for measurement of pulmonary function in rats exposed to chemicals in utero. This model will also be used to assess the effects of in utero exposure to mercury on the developing respiratory tract.